Evidence map›Paper›PMID 38437868›Full record

ArticleThe Journal of clinical endocrinology and metabolism2024

Mineralocorticoid Receptor and Aldosterone: Interaction Between NR3C2 Genetic Variants, Sex, and Age in a Mixed Cohort.

Mahyar Heydarpour, Wasita W Parksook, Luminita H Pojoga, Gordon H Williams, Jonathan S Williams

Registry-linked trialOpen access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The Journal of clinical endocrinology and metabolism, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03029806 (Lysine-specific Demethylase 1 and Salt-sensitivity in Humans), which is not on this map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
0.7field-weighted citation impact, top 29% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT03029806 naactive not recruitingnot on this map

Lysine-specific Demethylase 1 and Salt-sensitivity in Humans

TypeinterventionalSponsorBrigham and Women's HospitalRan2017 to 2026Enrolled88ConditionsHealthy SubjectsArmsAldosterone response to AngII LS, Renal blood flow response to salt, Vascular Stiffness
3 · Its place in the literature

Who cites it

4 citing papers in PubMed, 2 citations in OpenAlex.

  1. Review
  2. Cardioprotective Potential ofCurrent drug targets · 2026
    Article
  3. Observational
  4. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors at 1 institution in 2 countries.

Mahyar HeydarpourDivision of Endocrinology, Diabetes and Hypertension, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.ORCID 0000-0002-5741-367X
Wasita W ParksookDivision of Endocrinology, Diabetes and Hypertension, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Luminita H PojogaDivision of Endocrinology, Diabetes and Hypertension, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Gordon H WilliamsDivision of Endocrinology, Diabetes and Hypertension, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Jonathan S WilliamsDivision of Endocrinology, Diabetes and Hypertension, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.ORCID 0000-0001-7152-765X
Brigham and Women's Hospital · US

Funding

SCOR MOLECULAR GENETICS OF HYPERTENSIONP50HL055000 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI WILLIAMS, GORDON H · 1996 to 2005
$13.5M
TRAINING PROGRAM IN HYPERTENSIONT32HL007609 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI ADLER, GAIL KURR · 1985 to 2022
$10.2M
Epigenetic regulation of aldosterone and salt sensitivity in hypertensionR01HL127146 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI WILLIAMS, JONATHAN S. · 2016 to 2020
$3.3M
Caveolin-1 and vascular dysfunctionR01HL104032 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI POJOGA, LUMINITA · 2010 to 2014
$2.1M
American Heart Association GRNT20500000NHLBI NIH HHS P50 HL055000NHLBI NIH HHS R01 HL104032NHLBI NIH HHS R01 HL127146NHLBI NIH HHS T32 HL007609NIH HHS R01-HL-127146
6 · The paper itself

Abstract

contextHypertension, a prevalent cardiovascular risk, often involves dysregulated aldosterone and its interaction with the mineralocorticoid receptor (MR). Experimental designs in animal models and human cohorts have demonstrated a sex and age dependency of aldosterone secretion that expands our pathophysiologic understanding.

objectiveThis study explores the genetic variation of NR3C2, which encodes MR, in relation to aldosterone, considering age, sex, and race.

methodsIncorporating 720 Caucasians and 145 Africans from the HyperPATH cohort, we investigated the impact of rs4835490, a single nucleotide risk allele variant, on aldosterone levels and vasculature.

resultsNotably, a significant association between rs4835490 and plasma aldosterone under liberal salt conditions emerged in individuals of European ancestry (P = .0002). Homozygous carriers of the risk A allele exhibited elevated plasma aldosterone levels (AA = 8.1 ± .9 vs GG = 4.9 ± .5 ng/dL). Additionally, aldosterone activation through posture (P = .025) and urinary excretion (P = .0122) showed notable associations. Moreover, genetic interactions with race, sex, and age were observed. Caucasian females under 50 years displayed higher plasma aldosterone, urine aldosterone, and posture aldosterone with the AA genotype compared to females over 50 years, suggesting a potential connection with menopausal or estrogen influences. Interestingly, such age-dependent interactions were absent in the African cohort.

conclusionOur study highlights the significance of the NR3C2 genetic variation and its interplay with age, sex, and race in aldosterone activation. The findings point toward an estrogen-modulating effect on MR activation, particularly in women, underlining the role of aldosterone dysregulation in hypertension development. This insight advances our comprehension of hypertension's complexities and opens avenues for personalized interventions. Clinical Trial Registration Number: NCT03029806 (registered January 24, 2017).

Indexed as

AldosteronePolymorphism, Single NucleotideReceptors, MineralocorticoidWhite PeopleAdultAgedAge FactorsBlack PeopleCohort StudiesFemaleHumansHypertensionMaleMiddle AgedSex FactorsAldosteroneNR3C2 protein, humanReceptors, Mineralocorticoidagealdosteronehypertensionmineralocorticoid receptorNR3C2 genesex

Identifiers

PMID38437868
PMCPMC11651684
OpenAlexW4392756253

What OpenQuestion holds

Textmetadata
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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.